With optical detection system, an object can be detected to gain detailed analysis information, in which the application of surface plasmon waves is to implement analysis of the object through the Surface Plasmon Waves activated by light. Currently, the application is widely applied to biological detection and its molecular dynamics research including biosensor, immunodiagnosis and dynamic analysis of antibody and antigen. Through the chemical binding specificity of the antigen and its corresponding antibody, surface plasmon resonance is mainly applied to the dynamic analysis of the chemical binding between antibody and antigen in the research of biomedical science. The derivative applications include the detection of the existence of biomolecule, detection of subspecies of certain pathogenic bacteria, and detection and categorization of certain virus, among which the detection of the existence of biomolecule is currently the major derivative application of surface plasmon waves in biomedical science, such as inflammatory biomarker, the detection of cardiovascular disease using C-reactive protein, the detection of subspecies of certain pathogenic bacteria, and detection and categorization of certain virus.
The basic framework of a surface plasmon wave sensor is a sensing device that detects a change of the resonance condition between an incident light beam and surface plasmon wave on the interface of metal and dielectrics, and the change of the resonance is caused by the refractive index change of the dielectrics, which can be a result of antigen capture or molecular binding, molecular folding, deformation, or any other changes of the tested material close to or on the interface.
The change can be gained from measuring the optical property of the reflected light beam. Regarding the measurement on different optical properties of the reflected light beam, the measuring modes can be classified as angle, amplitude, wavelength, and phase modes. As for the operation procedure, though the measuring modes of amplitude and phase are static, the light path of the incident light beam needs to be adjusted before implementing measurement to receive the maximum sensitivity: the incident angle of the laser beam to obtain the largest change in amplitude with the refractive index change of dielectric substance, or the resonance angle for phase mode has to be located. When the system design does not allow incident angle adjustment, the detectable range of refractive index and sensitivity will be much restricted. Only when the system is operated under wavelength mode, a satisfied measuring dynamic range can be gained without changing the incident angle, except that the sensitivity is not as good as phase mode measurement. Moreover, the angle measuring mode is inherently dynamic, the incident angle of the light beam needs to be scanned repetitively during the measurement.
Traditional surface plasmon resonance instruments implementing corresponding rotation using two-arm rotating stage, in order to achieve the capability of adjusting the incident angle of the light beam. However, there are several disadvantages:    a. The incident light source and the receiving terminal are not fixed, which will limit the size, weight, and complexity of the light source system and the optical detection system. This also means that a detection method of a phase mode and an amplitude mode will be restricted.    b. The resolution, accuracy, and stability, of a rotation stage are not as good as a linear motorized stage. Besides, two rotation stages are not cost effective compared to a linear stage.    c. Due to the structural limitation of optical elements, the coupling side of the coupling prism is mainly oriented vertically. When matching oil is used to couple a glass slide and the prism, the matching oil is easy to evaporate after a long time use. As a result, the system stability and measurement consistency in the long time use are not easy to maintain.    d. The vertical orientation of the prism coupling face is not suitable for the design and operation of a microfluidics chip.    e. The vertical orientation of prism coupling face cannot be incorporated into an image system, particularly a microscopy system, because the design of vertical light path for image capture is mainly adopted in a microscopy system.
There is another way to adjust the incident angle of the light beam by incorporating a galvo mirror scanning system. In this method, the light path of the reflected beam will be deflected from the designed incidence angle of the optical elements and detectors in the detection system. This beam deflection caused by incident angle tuning will result in the impossibility of implementing phase detection. However, phase detection usually has higher sensitivity.
In the last few years, although the models of all kinds of detection modes have different advantages, there is still a lack of the design that can integrate several modes into one device. With current devices, operation modes (resonance angle mode and amplitude measuring mode) with a large dynamic range usually cannot meet the requirement of high sensitivity, and the incident angle of the light beam in a device performing a phase mode is usually fixed; therefore, its dynamic range is extremely small.
U.S. Pat. No. 7,265,844 discloses a horizontal surface plasmon resonance instrument that is claimed to be able to adjust the incidence angle through a complicated mechanical motion and track with special curves, and thus fix the position of the light source and the optical detection unit. However, the accuracy and stability are not satisfying.
Moreover, FIG. 1 is also a prior art, which is the illustration of surface Plasmon wave detection system disclosed by the inventor of the present invention. As illustrated, the surface Plasmon system 100 includes a light source unit 110, a control unit 120, a detection unit 130 and a process unit 140.
The light source unit 110 includes: a semiconductor laser 111, a polarizing beam splitter 112 and a half-wave plate 113, used to direct the light into the control unit 120.
The control unit 120 includes: a motorized stage 121, a right angled triangle mirror 122, two-dimensional parabolic mirror 123a and 123b and a hemispherical lens 124. The light is directed by the triangle mirror 122 into the two-dimensional parabolic mirror 123a. The two-dimensional parabolic mirror 123a first directs the light into the hemisphere lens 124, and the hemisphere lens 124 then directs the light into the two-dimensional parabolic mirror 123b. At last, the light is directed into the triangle mirror 122 through the two-dimensional parabolic mirror 123b and output to the detection unit 130.
The detection unit 130 includes: a non-polarizing beam splitter 131, a polarizing beam splitter 132, a detection element 133, an amplifier 134, a wave plate 135 and a control element 125. Through the optical property detected by the detection unit 130, the signal is sent to the process unit 140 for further analysis.
Users, through the adjustments of motorized stage 121 and the two-dimensional parabolic mirror 123a and 123b, can detect the object to maintain the incidence angle of laser at the largest angle that causes the largest change in refraction index in amplitude, or the best resonance angle for energy coupling to detect the changes caused by the refractive index of the medium.
However, hemisphere lens and the two-dimensional mirror will both cause the complexity in light path adjustment and beam path deflection after long time operation. Slight deflection in the light path of the incident light will cause an error in the incidence angle and the enlargement of deflection in the light path. This shortage will cause difficulty in the detection of the optical phase and the resonance angle for the receiving terminal, which might cause a detection error or, in the worst scenario, a situation of not being able to implement the detection. Moreover, the system needs to be used with two two-dimensional off-axis parabolic mirror 123a and 123b at the same time; This will cause much more difficulty in the adjustment of positions of the three optical components. Therefore, users cannot easily scan the full incident angle without changing the light path to the detection unit 130. When the implementation of the angle scanning with a large range without the occurrence of light path deflection is desired, it will take a long time to adjust the relative positions of the coupling prism and two off-axis parabolic mirrors as well as the path incident light. Moreover, due to the focusing effect of the hemisphere lens 124 and the two-dimensional parabolic mirror 123a and 123b, the activation spot of the incident light will be very small which can only be used for the detection of single spot or single channel. Moreover, this design is not equipped with a mirror that directs horizontal propagation light into vertical propagation, so it's not easy to be integrated into a microscopy system.